DESCRIPTION: (Applicant's Description) There has been insufficient research on how best to translate effective smoking cessation treatments into efficient public health interventions. Public health interventions reach many through proactive recruitment but are efficacious with few, while clinic- based interventions reach few, (reactive and self-selected), but are effective. Lifetime comorbid risk can also attenuate the efficiency of both clinical and public health interventions. A significant proportion of adult smokers are at high risk for smoking treatment failure by virtue of comorbidity (i.e., nicotine dependent, psychiatric comorbidity, multiple psychosocial barriers to quitting). The influence of familial, prenatal nicotine exposure, and early childhood risk factors on adult response to treatment has not been examined in any study we are aware of. We will recruit subjects proactively from the transgenerational longitudinal National Collaborative Perinatal Project (NCPP) who are now aged 34 to 40 - the G2 generation. The G2's have been followed since birth and detailed information is available on prospective prenatal, postnatal, and early childhood risk factors. During baseline structured interviews of the (32 generation of the NCPP, we will also gather expensive lifetime and concurrent data on adult smoking patterns and co- morbid risk factors for smoking treatment failure. Thus we propose to investigate the relationship between familial, early childhood and adult lifetime risk factors and response to treatment in a proactively recruited sample from the NCCP longitudinal cohort. This study also seeks to bridge the gap between public health and clinical interventions by coupling the advantages of a public health approach (proactive reach) with the advantages of a more intensive clinical strategy (multi-modal, sustained contact). The primary aims are: 1) to compare the efficacy of two smoking cessation interventions, Brief Telephone Counseling (BTC) and Sustained Multi-Modal Counseling (SMC) in a randomized trial of 780 subjects followed for 24 months after baseline and, 2) to examine the relationship between early childhood and adult lifetime high and low risk profiles and treatment response. We will also examine cost-effectiveness and conduct program and process to outcomes analysis to examine the dosage of intervention delivered and received. A transdisciplinary approach at the interface between clinical and public health interventions, using a common community sample drawn from the trans- generational NCPP study, can advance the understanding of basic bio- behavioral mechanisms in nicotine dependence, lifetime risk factors and the interactions of these variables with treatment response.